Endosomal lipid flippases and their related diseases
Endosomal lipid flippases and their related diseases
复制标题
内体脂质翻转酶及其相关疾病
DOI：
10.1080/19336950.2015.1062332
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Hiroyuki Arai
中科院分区：
文献类型：
--
作者：
Shoken Lee;Tomohiko Tatguchi;Hiroyuki Arai
在真核细胞膜中，磷脂不对称地分布在脂质双分子层的两个小叶之间。例如，质膜的胞外小叶富含磷脂酰胆碱和鞘磷脂，而质膜的胞内小叶富含磷脂酰丝氨酸（PS）和磷脂酰乙醇胺。PS在PM中的不对称分布对细胞寿命至关重要，因为PM的细胞外小叶中的PS被吞噬细胞识别为“吃我”信号。在细胞内，PM胞质小叶中的高PS浓度对于通过募集蛋白激酶C和Akt等信号分子促进各种细胞事件至关重要。磷脂的不对称分布被认为部分是由磷脂转位或“翻转”产生的。负责翻转酶活性的蛋白质是IV型p型atp酶（p4 - atp酶）。p型ATP酶是使用ATP水解作为能量来源的多跨跨膜泵。P型atp酶在催化循环中对保守的天冬氨酸残基进行自磷酸化，因此被称为“P”型。p4 - atp酶的独特之处在于它们是磷脂转运体，而其他类型的p型atp酶是离子转运体。
In eukaryotic cell membranes, phospholipids are asymmetrically distributed between the two leaflets of the lipid bilayer. For example, the extracellular leaflet of the plasma membrane (PM) is enriched with phosphatidylcholine and sphingomyelin, while the cytosolic leaflet of the PM is enriched with phosphatidylserine (PS) and phosphatidylethanolamine. The asymmetric distribution of PS in the PM is crucial for cell life, since PS in the extracellular leaflet of the PM is recognized as an “eat-me” signal by phagocytes. Inside the cells, a high PS concentration in the cytosolic leaflet of the PM is essential to facilitate various cellular events through the recruitment of signaling molecules such as protein kinase C and Akt.The asymmetric distribution of phospholipids is believed to be generated in part by phospholipid translocases, or “flippases.” The proteins responsible for flippase activity are type IV P-type ATPase (P4-ATPases). P-type ATPases are multispan transmembrane pumps that use ATP hydrolysis as an energy source. P-type ATPases undergo autophosphorylation of a conserved aspartate residue during the catalytic cycle, hence the designation of “P”-type. P4-ATPases are unique in that they are phospholipid transporters whereas other types of P-type ATPases are ion transporters.